DESCRIPTION: (Applicant's abstract) We have developed a new ink-jet technology approach to the synthesis of DNA fragments (oligonucleotides) on glass or silicon chips. These DNA chips provide the potential opportunity to analyze thousands or even tens of thousands of expressed genes simultaneously by molecular complimentarity or hybridization. Thus, for example, the differences in gene expression patterns between normal and cancer cells can readily be analyzed. These DNA chips also afford the opportunity to readily analyze the most widespread genetic marker scattered across human chromosomes, single base substitutions. Thus, an inexpensive, rapid and comprehensive approach to genetic mapping may be possible. To realize the enormous potential of oligonucleotide chips, we propose to: 1) characterize the quality of the oligonucleotides synthesized by the ink-jet technology, 2) use yeast as a model system to explore how the expression patterns of 6,000 genes operating as systems under varying conditions can be quantitated, and 3) use this technology to develop a rapid and comprehensive typing system for the highly polymorphic human transplantation antigen locus, HLA-B.